Cancer cells possess unique cellular signatures which signal the presence of the disease. This property can be potentially used as a marker to detect the presence of the cancer. Riboflavin Carrier Protein (RCP) is an estrogen induced growth and development specific protein. We hypothesize that serum levels of RCP can be used to accurately and non- invasively detect ovarian epithelial cancer and other cancers unique to women such as those of the breast, endometrium and cervix. In this project we will test this hypothesis using ovarian epithelial cancer as a model system. In a preliminary study of 6 women, we found that mean RCP levels were 3.5 ng/ml for state I and 11.2 ng.m. for state III ovarian cancer, as compared to 0.7 ng/ml for healthy subjects. Although the study size is small, the differences are highly statistically significant with p values for difference less than 0.05. In the present proposal, we will prospectively confirm our preliminary results in a case control study. We will recruit incident ovarian cancer cases from clinics at LSU Health Sciences Center, University Hospital and Memorial Medical Center. Control subjects not having any cancer will be recruited from Gynecology clinics and will be matched 1.1 for race, age, menopausal status and if pre-menopausal, for day of menstrual cycle. Serum RCP levels will be tested on both cases and controls at entry into the study. We will attempt to confirm our preliminary data that serum, RCP levels can accurately detect early ovarian epithelial cancer and predict its stage. We will also measure the serum levels of CA-125, a marker that is currently being used even though it is elevated in only about 50% of ovarian cancers. We will compare performance of RCP test with CA-125 test in order to evaluate the superiority of the former in predicting early ovarian cancer. We will compare performance of RCP test with CA-125 test in order to evaluate the superiority the former in predicting early ovarian cancer. Finally, using immunohistochemical techniques, we will characterize expression patterns of RCP in epithelial ovarian cancer tumor tissue. Our preliminary studies suggest a role of RCP as a molecular signature indicative of the present of ovarian cancer. The RCP test will be a valuable application of the use of cancer cell signatures as detection markers, which is a critical component of the 2001 Bypass Budget Document of NCI.